Related Experiment Video
Updated: Jun 27, 2026
10:09
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
Published on: January 7, 2019
Kinetic mechanisms for overexpression insensitivity and oncogene cooperation
Stefan Legewie1, Christine Sers, Hanspeter Herzel
1Institute for Theoretical Biology, Humboldt University, Berlin, Germany. s.legewie@biologie.hu-berlin.de
FEBS Letters
|December 9, 2008
Summary
Even strong signaling protein overexpression typically does not trigger cell division. Kinetic modeling reveals that basal Ras signaling can be insensitive to Ras overexpression, suggesting a tumor suppression mechanism.
Area of Science:
- Cellular signaling pathways
- Cancer biology
- Systems biology
Background:
- Mitogenic signaling cascades control cell division, and their aberrant activation drives tumorigenesis.
- Despite this, wild-type protein overexpression often fails to induce deregulated proliferation, indicating inherent insensitivity in basal signaling states.
Purpose of the Study:
- To investigate the insensitivity of basal Ras signaling to protein overexpression.
- To identify potential tumor suppression mechanisms related to signaling pathway dynamics.
- To understand how seemingly minor genetic alterations cooperate in carcinogenesis.
Main Methods:
- Kinetic modeling of the core Ras signaling cycle.
- Computational analysis of signaling pathway dynamics.
Main Results:
- Basal Ras signaling can exhibit insensitivity to Ras protein overexpression.
- Phenotypically silent overexpression events within signaling cascades can collectively contribute to carcinogenesis.
- Demonstrated a potential tumor suppression mechanism inherent in the Ras signaling network.
Conclusions:
- A systems-level understanding is crucial for comprehending tumor formation.
- The Ras signaling pathway possesses intrinsic mechanisms that can confer resistance to oncogenic transformation.
- Cooperative effects of multiple genetic alterations are critical in driving cancer development.
Related Concept Videos
01:33Cancer-Critical Genes I: Proto-oncogenes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:33Cancer-Critical Genes I: Proto-oncogenes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:51Mechanisms of Retrovirus-induced Cancers
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...